Student outbreak response teams: lessons learned from a decade of collaboration.

OBJECTIVES: Student response teams within colleges of public health effectively address important concerns for two stakeholders. For universities, students learn the fundamentals of field epidemiology and provide popular training and networking opportunities. For health departments, students serve as surge capacity as trained workforce available during outbreak investigations and potentially for routine tasks. STUDY DESIGN: This paper describes the interaction between a student response team and several health departments utilizing specific examples to demonstrate the various roles and activities students can fulfill. Lessons learned from both University team leaders and the various health departments are also included. METHODS: The program evolved over time, beginning with a needs assessment of local health departments and a determination of student training needs, collection, and confidential transmission of data, and interviewing techniques. Over the last decade students have worked on outbreak investigations, case-control studies, program evaluations, and in-field responses. RESULTS: Since 2005, over 200 public health graduate students have contributed more than 1800 h investigating 62 separate disease outbreaks in Arizona. In addition, over the past four years students also worked an additional 2500 h to assist county health departments in routine enteric investigations, specifically for Campylobacter and Salmonella. Best practices and lessons learned found that communication, preplanning and a willingness to collaborate increased the learning opportunities for students and ability for health departments to increase their capacity both during an emergency and for routine work. CONCLUSIONS: Establishment of a student response team (1) trains students in field experiences; (2) creates trained surge capacity for health departments; (3) increases collaboration between schools of public health and state/local health departments; (4) establishes a way to share funding with a local health department; and (5) increases the number of students being placed in health departments for projects, internships, and jobs following graduation.

Assessing risk factors of sporadic Campylobacter infection: a case-control study in Arizona.

Case-control studies of sporadic Campylobacter infections have predominately been conducted in non-Hispanic populations. In Arizona, rates of campylobacteriosis have been historically higher than the national average, with particularly high rates in Hispanics. In 2010, health departments and a state university collaborated to conduct a statewide case-control study to determine whether risk factors differ in an ethnically diverse region of the United States. Statistically significant risk factors in the final multivariate model were: eating cantaloupe [odds ratio (OR) 7·64], handling raw poultry (OR 4·88) and eating queso fresco (OR 7·11). In addition, compared to non-Hispanic/non-travellers, the highest risk group were Hispanic/non-travellers (OR 7·27), and Hispanic/travellers (OR 5·87, not significant). Results of this study suggest Hispanics have higher odds of disease, probably due to differential exposures. In addition to common risk factors, consumption of cantaloupe was identified as a significant risk factor. These results will inform public health officials of the varying risk factors for Campylobacter in this region.

Design and validation of a multiplex specific primer-directed polymerase chain reaction assay for killer-cell immunoglobulin-like receptor genetic profiling.

Current methodologies for the analysis of the killer-cell immunoglobulin-like receptor (KIR) locus utilize specific primer-directed polymerase chain reaction (SSP-PCR), which require a wide range of DNA input, multiple reaction conditions, and up to 16 individual reactions. We have developed and validated a multiplex SSP-PCR method for the genetic analysis of the KIR locus. Design and optimization of four multiplex groups targeting 14 genes and their alleles on the KIR locus has been completed. Each multiplex group contains PCR products that differ in size by a minimum of 15 bp to allow sufficient fragment length resolution for size discrimination by gel electrophoresis. This assay allows for efficient genotyping of the KIR locus while requiring a minimum amount of DNA input, utilizing the simplicity of SSP-PCR.

Impact of a community-based breast cancer screening program on Hopi women.

OBJECTIVE: To examine changes in breast cancer knowledge, attitudes, beliefs and behaviors following implementation of a tribal run CDC Breast and Cervical Cancer Program (BCCP), we report 2006 survey results from Hopi women and contrast findings with 1993 survey data and BCCP reports. METHODS: Community meetings, focus groups, and researchers jointly developed a culturally appropriate survey instrument. Hopi women randomly selected from Tribal enrollment lists were interviewed in-person by Hopi interviewers; 250 women ≥ age 18 participated (87% response) between June and December, 2006. RESULTS: Among women 40+, 77.5% reported ever having had a mammogram and 68.9% reported having done so within the past 2years, an increase from 45.2% and 46% self-reported in 1993. Compared to 1993, more women in 2006 (88.1% vs. 59%) believed that a mammogram can detect cancer and more than 90% now believe that early detection of cancer can save lives. Women reported a preference (60%) for receiving health care at the Hopi BCCP. Survey results were validated using programmatic data which estimated 76.6% of Hopi women had received mammography screening. CONCLUSION: Implementation of a tribal run BCCP has resulted in a substantial increase in mammography screening on the Hopi reservation.

The effects of repeated restraint stress on energy balance and behavior of mice with selective deletion of CRF receptors.

Mice subjected to restraint stress (RRS) daily for 3 days lose weight. Once stress ends they are slow to recover the weight loss and exhibit increased anxiety and hypothalamus-pituitary-adrenal (HPA) activity in response to novel stressors. We tested the effect of RRS in mice deficient in corticotropin releasing factor receptor one (CRFR1-KO) or two (CRFR2-KO). Wild type (WT) and CRFR2-KO, but not CRFR1-KO, mice lost weight during RRS. All adrenalectomised mice lost weight and CRFR2-KO controls stopped gaining weight on the days of RRS. WT RRS mice returned to the weight of their controls 8 days after restraint. CRFR2-KO mice showed high levels of anxiety in an elevated plus maze (EPM) 11 days after RRS and in a light/dark choice test 14 days after RRS. CRFR1-KO mice displayed low anxiety in both tests, but RRS decreased EPM exploration. By contrast, exploration increased in RRS ADX mice. Testing in the EPM increased serum corticosterone level in all WT and CRFR2-KO mice. Corticosterone increased in RRS CRFR1-KO mice compared with their controls. These results suggest that CRFR1 are required for stress-induced weight loss, but that hyper-reactivity of the HPA axis in RRS mice exposed to a subsequent novel stress is independent of CRFR1.

Reducing achievement gaps in undergraduate general chemistry could lift underrepresented students into a "hyperpersistent zone".

Students from underrepresented groups start college with the same level of interest in STEM majors as their peers, but leave STEM at higher rates. We tested the hypothesis that low grades in general chemistry contribute to this "weeding," using records from 25,768 students. In the first course of a general chemistry series, grade gaps based on binary gender, race/ethnicity, socioeconomic status, and family education background ranged from 0.12 to 0.54 on a four-point scale. Gaps persisted when the analysis controlled for academic preparation, indicating that students from underrepresented groups underperformed relative to their capability. Underrepresented students were less likely than well-represented peers to persist in chemistry if they performed below a C-, but more likely to persist if they got a C or better. This "hyperpersistent zone" suggests that reducing achievement gaps could have a disproportionately large impact on efforts to achieve equity in STEM majors and professions.

Early and late stimulation of ob mRNA expression in meal-fed and overfed rats.

ob protein is hypothesized to be a circulating feedback signal in the regulation of energy balance. Obese, overfed rats have high levels of ob mRNA expression and suppressed voluntary food intake, indicating the presence of a potent satiety factor. The objectives of this experiment were to determine whether feeding rats their normal daily intake in three meals, compared with ad libitum feeding, increased ob mRNA expression and to determine the degree of obesity required to stimulate expression of ob mRNA. Rats were fed ad libitum, were tube-fed their normal intake in three meals a day, or were tube-fed twice normal intake, ob mRNA was measured by Northern blot analysis after 0, 2, 7, 14, 21, and 32 d of tube-feeding. After only 2 d ob mRNA was threefold higher in tube-fed animals than in ad libitum controls. By day 21 there was a further increase in ob mRNA expression in overfed rats which were at 130% control weight. These results suggest that a metabolic consequence of meal-feeding increases ob mRNA expression in the absence of increased food intake or weight gain. There is a further increase in ob mRNA expression once significant obesity is established.

Functional analysis of human ornithine decarboxylase alleles.

It has been known for > 10 years that there are two alleles of the human ornithine decarboxylase (ODC) gene, defined by a polymorphic PstI RFLP in intron 1. We have sequenced a large portion of each of the two alleles, including some of the 5' promoter region, exon 1, intron 1, and exon 2, and determined that a single nucleotide polymorphism at base +317 (relative to transcription start site) is responsible for the presence or absence of the PstI restriction site. We have developed two genotyping assays, a PCR-RFLP assay and a high-throughput TaqMan-based method, and determined the ODC genotype distribution in >900 North American DNA samples. On the basis of its location between two closely spaced Myc/Max binding sites (E-boxes), we speculated that the single nucleotide polymorphism at base +317 could have functional significance. Results of transfection assays with allele-specific reporter constructs support this hypothesis. The promoter/regulatory region derived from the minor ODC allele (A allele) was more effective in driving luciferase expression in these assays than the identical region from the major allele (G allele). Our results suggest that individuals homozygous for the A allele may be capable of greater ODC expression after environmental exposures, especially those that up-regulate c-MYC expression.

Partial purification of biologically active, low molecular weight, human antihemophilic factor free of Von Willebrand factor. I. Partial characterization and evidence for disulfide bond(s) susceptible to limited reduction.

Partially purified (approx. 5000-fold), low molecular weight human antihemophilic factor, free of detectable Von Willebrand factor (ristocetin cofactor activity or Von Willebrand antigen), was prepared from fresh citrated plasma by limited reduction with 1 mM dithiothreitol and chromatography on Sepharose CL-4B, Sephadex G-100, and polyelectrolyte E-5. The ratio of antihemophilic factor activity to Von Willebrand factor activity or antigen was greater than 27 000 : 1. The antihemophilic factor activity could be neutralized with homologous antibody and could be further increased with thrombin. The Mr (approx. 116 000) was determined by calibrated gel permeation chromatography, electrophoresis in 5% polyacrylamide gels with sodium dodecyl sulfate and by electrophoresis in large-pore acrylamide gels without it. Since the low Mr antihemophilic factor could be prepared by treating fresh rather than fresh-frozen plasma with dithiothreitol, it was concluded that partial reduction of the antihemophilic factor with this reagent helped to maintain the antihemophilic factor in a low Mr form. When iodo[l-14C]acetamide was used to alkylate the reduced plasma proteins prior to purification, the molecular weight of the purified antihemophilic factor remained low despite numerous purification steps. By this means, one of four radioactive proteins (Mr 116 000) in the final preparation was bound specifically to homologous antihemophilic factor antibody and attributed to 14C-labeled antihemophilic factor. While the data suggest that antihemophilic factor in fresh plasma contains one or more dithiothreitol-sensitive intramolecular disulfide bonds, the possibility of disulfide linkages with other proteins(s) cannot be excluded.

Partial purification of biologically active, low molecular weight, human antihemophilic factor free of Von Willebrand factor. II. Further purification with thiol-disulfide interchange chromatography and additional evidence for disulfide bonds susceptible to limited reduction.

Thiol-disulfide interchange chromatography was used in the preparation of partially purified (approx. 17 000-fold) low molecular weight, Mr approximately or equal to 115 000, human antihemophilic factor essentially free of Von Willebrand factor. This antihemophilic factor was prepared from fresh plasma which had undergone limited reduction with 1 mM dithiothreitol and was subsequently reacted with 2,2'-dipyridyl disulfide, a sulfhydryl reagent which readily undergoes disulfide exchange. Exchange of protein-2-pyridyl mixed disulfide with thiopropyl-Sepharose resulted in the chromatographic adsorption of approx. 96% of the coagulant activity, of which approx. 20% subsequently eluted with 1.0 mM dithiothreitol. After reductive displacement from the thiopropyl-Sepharose the antihemophilic factor could be S-alkylated with iodo-[1-14]acetamide. The ratio of coagulant activity to Von Willebrand factor-antigen activity was greater than 30 000 : 1. In contrast, reduced antihemophilic factor was alkylated with iodoacetamide prior to chromatography as a control, and showed no exchange with the thiopropyl-Sepharose, eluting quantitatively in the breakthrough volume. These studies reinforce our previous results (Harris, R.B., Newman, J. and Johnson, A.J. (1981) Biochim. Biophys. Acta 668, 456-470) that partial reduction with dithiothreitol exposes critical sulfhydryl groups which, when alkylated, maintains the antihemophilic factor in a low molecular weight form without inactivating procoagulant activity.

Voluntary wheel running decreases adipose tissue mass and expression of leptin mRNA in Osborne-Mendel rats.

The purpose of this study was to assess the effects of voluntary wheel running on the expression of leptin mRNA in rats that are either sensitive (OM) or resistant (S5B/Pl) to diet-induced obesity. Male OM and S5B/Pl rats had ad libitum access to standard rodent diet and water. At 3-5 weeks of age, animals of both strains were randomly assigned to either an exercise or sedentary control group. The exercise groups had 24-h access to a running wheel, and they trained for 7 weeks. During weeks 1-4, animals in both OM and S5B/Pl exercise groups progressively increased their running. During weeks 5-7, S5B/Pl exercisers tended to run more than did OM (approximately 60 vs. 45 km/week), but by the end of the study both groups had an equally greater heart weight (mg/g body weight) and planteris citrate synthase activity than their sedentary controls. Oral glucose tolerance tests performed during the last week of training revealed that compared with their appropriate controls, insulin sensitivity was enhanced (P < 0.05) in OM but not in the S5B/Pl wheel-running groups. Inguinal, epididymal, and retroperitoneal fat pads weighed less in the running than in the nonrunning groups of both strains (P < 0.01). Additionally, exercised animals had an increased percentage of smaller cells (40-60 microm; P < 0.05) and a decreased percentage of larger cells (120-160 microm; P < 0.05) in the epididymal fat depot. Epididymal leptin mRNA measured by Northern blot analysis was reduced in the exercise-trained rats of both strains (P < 0.05). Furthermore, serum leptin was reduced in exercise-trained compared with the control animals of both strains. In comparison to S5B/Pl, control OM animals exhibited both a higher expression and higher circulating levels of leptin (P < 0.05). While serum leptin levels were decreased and food intake was increased in the exercise-trained animals of both strains (P < 0.05), the exact relationship between exercise, leptin, and food intake in this rat model of dietary obesity remains to be determined. Nonetheless, these results suggest that the expression and secretion of leptin can be influenced by exercise training and that these changes (i.e., reduced expression and secretion of protein) can occur independently of changes in whole-body insulin sensitivity and susceptibility to diet-induced obesity.

Genomic resources notes accepted 1 August 2014-30 September 2014.

This article documents the public availability of (i) transcriptome sequence data, assembly and annotation, and single nucleotide polymorphisms (SNPs) for the cone snail Conus miliaris; (ii) a set of SNP markers for two biotypes from the Culex pipiens mosquito complex; (iii) transcriptome sequence data, assembly and annotation for the mountain fly Drosophila nigrosparsa; (iv) transcriptome sequence data, assembly and annotation and SNPs for the Neotropical toads Rhinella marina and R. schneideri; and (v) partial genomic sequence assembly and annotation for 35 spiny lizard species (Genus Sceloporus).

Heparin binding domain peptides of antithrombin III: analysis by isothermal titration calorimetry and circular dichroism spectroscopy.

The serine proteinase inhibitor antithrombin III (ATIII) is a key regulatory protein of intrinsic blood coagulation. ATIII attains its full biological activity only upon binding polysulfated oligosaccharides, such as heparin. A series of synthetic peptides have been prepared based on the proposed heparin binding regions of ATIII and their ability to bind heparin has been assessed by CD spectrometry, by isothermal titration calorimetry, and by the ability of the peptides to compete with ATIII for binding heparin in a factor Xa procoagulant enzyme assay. Peptide F123-G148, which encompasses both the purported high-affinity pentasaccharide binding region and an adjacent, C-terminally directed segment of ATIII, was found to bind heparin with good affinity, but amino-terminal truncations of this sequence, including L130-G148 and K136-G148 displayed attenuated heparin binding activities. In fact, K136-G148 appears to encompass only a low-affinity heparin binding site. In contrast, peptides based solely on the high-affinity binding site (K121-A134) displayed much higher affinities for heparin. By CD spectrometry, these high-affinity peptides are chiefly random coil in nature, but low microM concentrations of heparin induce significant alpha-helix conformation. K121-A134 also effectively competes with ATIII for binding heparin. Thus, through the use of synthetic peptides that encompass part, if not all, of the heparin binding site(s) within ATIII, we have further elucidated the structure-function relations of heparin-ATIII interactions.

The regulation of total body fat: lessons learned from lipectomy studies.

Surgical removal of body fat (partial lipectomy) is a means of directly reducing fat such that metabolic and behavioral responses can be readily attributed to the lipid deficit. If total body fat is regulated, then lipectomy should trigger compensatory increases in nonexcised white adipose tissue (WAT) mass and/or regrowth at excision sites. Many species, including laboratory rats and mice, show lipectomy-induced compensatory recovery of body fat. Those animals exhibiting naturally occurring annual adiposity cycles, such as ground squirrels and hamsters, do so most impressively reaching seasonally appropriate body fat levels indistinguishable from controls. Reparation of the lipid deficit occurs without an increase in food intake, and generally through enlargement of non-excised WAT mass, rather than regrowth of excised WAT. A body fat regulatory system involving humoral and sensory neural inputs to the brain as well as sympathetic neural outputs from brain to adipose tissue is presented. Collectively, the lipectomy model appears useful for testing mechanisms controlling adiposity, or individual depot growth, and offers insight into how lipid stores fluctuate naturally.

Parabiosis between db/db and ob/ob or db/+ mice.

Genetically obese C57B1/6J-m db/db mice were parabiosed with either lean male db/+ or obese female ob/ob mice. Male db/db mice had lower serum leptin than females, and this was reflected in the amount of protein that crossed the parabiotic union into their partners. Eighteen days post operation, ob/ob partners of db/db mice had increased body temperature, lost 50% body weight and 60% body fat, but maintained carcass protein. The db/+ partners of db/db mice had a normal gut content and (by implication) food intake, did not raise their body temperature, but lost significant amounts of both lean and fat tissue during 25 days of parabiosis. The differences between the db/+ and ob/ob partners of db/db mice may be caused by leptin inhibiting growth of male mice, but not of female mice that are on a slower growth curve, or by the excess lipid in ob/ob mice sparing body protein. The db/db partners of ob/ob mice lost a small amount of body fat, but carcass protein was increased by 30%, compared with their controls. These results imply that leptin stimulated release of a circulating growth factor, possibly through activation of the long-form leptin receptor, in ob/ob partners of db/db mice.

Cytoplasmic estrogen receptors and estrogen concentrations in bovine uterine endometrium.

Specific cytoplasmic binding of 17beta-[3H]estradiol ([3H]E2beta) by unoccupied receptors in bovine uterine endometrium was determined by saturation analysis and correlated with endometrium levels of E2beta in 21 cows. The concentrations of these estrogen receptors (ER) during the estrous cycle were significantly greater during proestrus, estrus, and postestrus (days 18-20 and 0-4 of the cycle) than during the midluteal period (days 10-12; P less than 0.05). These increases in ER concentration paralleled increases in endometrial and plasma E2beta concentrations. In a preliminary experiment involving six heifers killed during the estrous cycle, a comparison of the ER concentrations of the horns ipsilateral and contralateral to the corpus luteum showed no significant differences, as did a study of the dissociation constant of the steroid-receptor interaction during the estrous cycle and early pregnancy. The order of inhibition of cytoplasmic binding of [3H]E2beta by estrogens was as follows: E2beta greater than E1 greater than E2alpha greater than E3 at 4 C. The concentration of ER in six pregnant animals was higher on days 2-3 than on days 13-14 after insemination, which was similar to that found in cycling animals; however, the difference between days was not significant. Ovariectomy of two heifers resulted in slightly higher ER concentrations than in intact heifers, whereas immunization of two heifers with an E2beta conjugate resulted in levels 2-fold higher. In these altered animals plasma progesterone (P4) was nearly nondetectable. ER concentration was inversely related to the level of plasma P4 in cycling heifers (r = -0.58, P less than 0.01). Endometrial estrogen and plasma estrogen levels were also inversely correlated with plasma P4 levels (r = -0.65, P less than 0.01 and r = -0.48, P less than 0.05, respectively). Thus, if P4 level influences ER levels, the hormone may make the tissue less responsive to ovarian estrogens at such time as the luteal phase of the cycle and during pregnancy.

A leptin dose-response study in obese (ob/ob) and lean (+/?) mice.

This experiment determined the amount of leptin required to correct different abnormalities in leptin-deficient ob/ob mice. Baseline food intakes and body weights of lean (+/?) and obese (ob/ob) C57B1/6J mice were recorded for 7 days. An Alzet miniosmotic pump was placed in the peritoneal cavity of each mouse and delivered 0, 1, 2, 5, 10, or 42 microg/day human leptin for 7 days. In ob/ob mice, 2 microg leptin/day reduced food intake and body weight, and increased hypothalamic and brain stem serotonin concentrations. All fat pads were reduced 35-40% by 10 microg leptin/day, and liver weight, lipid, and glycogen decreased. Serum insulin and glucose were reduced in all leptin-treated ob/ob mice, and levels were normalized by 10 microg/day leptin. Low rectal temperatures of ob/ob mice were corrected by 10 and 42 microg/day leptin. These doses also increased brown adipose tissue uncoupling protein expression. The only responses in lean mice were a transient reduction in food intake and weight loss with 10 or 42 microg/day leptin. This study shows enhanced leptin sensitivity in ob/ob mice and suggests that increased temperature and sympathetic activity are indirect responses to high concentrations of protein.

Tea intake and squamous cell carcinoma of the skin: influence of type of tea beverages.

Differences in tea drinking habits are likely to vary by populations and could contribute to the inconsistencies found between studies comparing tea consumption and cancer risk. A population-based case-control study was used to evaluate how usual tea consumption patterns of an older population (n = 450) varied with history of squamous cell carcinoma (SCC) of the skin. A detailed tea questionnaire was developed to assess specific tea preparation methods and patterns of drinking. In this southwestern United States population, black tea was the predominant variety of tea consumed. We found no association between the broad definition of any tea consumption and skin SCC. However, the adjusted odds ratios (ORs) for hot and iced black tea intake were 0.63 [95% confidence interval (CI), 0.36-1.10] and 1.02 (95% CI, 0.64-1.63), respectively. Controls were more likely to report usually drinking strong hot tea (OR, 0.74; 95% CI, 0.53-1.03) with increased brewing time (P for trend = 0.03). Adjusting for brewing time, the association between skin SCC and hot black tea consumption suggests a significantly lower risk in consumers of hot tea compared to nonconsumers (OR, 0.33; 95% CI, 0.12-0.87). This is one of the first studies to explore the relation between different types of tea consumption and occurrence of human cancers. Our results show that tea concentration (strength), brewing time, and beverage temperature have major influences on the potential protective effects of hot black tea in relation to skin SCC. Further studies with increased sample sizes are needed to evaluate the interrelationships between preparation techniques, tea type, and other life-style factors.

Reproducibility and relative validity of a questionnaire to assess intake of black tea polyphenols in epidemiological studies.

Epidemiological studies suggest that tea drinking may reduce the risk of cardiovascular diseases and cancers. Although tea is an important source of antioxidant phytochemicals, variation in preparation techniques may translate to variation in antioxidant capacity. However, most large-scale epidemiological studies use regular food frequency questionnaires to estimate tea intake, and nationally available nutrient analysis databases do not include levels of black tea polyphenols. The Arizona Tea Questionnaire (ATQ) was designed as a tool for collecting more complete dietary tea consumption information, and a database was developed after analyzing 40 black tea samples (brewed, instant, and sun tea) for polyphenols. This study assesses the reliability and relative validity of the ATQ and polyphenol database. Relative validity of estimates of black tea consumption was tested by comparing the ATQ with the traditional Arizona Food Frequency Questionnaire and four days of food records. The ATQ was tested for reproducibility of estimates of black (hot and iced) tea consumption and levels of black tea polyphenol intake. Correlations between two measures of intake taken 2 months apart ranged from 0.72 for black hot tea to 0.86 for black sun tea. Mean intakes (range) of total flavonoids for black tea consumers were 80.8 (3.0-588.0) mg/day at the first ATQ and 102.4 (4.5-802.3) mg/day at the second ATQ (r = 0.83, P < 0.001). The ATQ provided highly reproducible estimates of both total tea consumption and individual tea polyphenol intake. This instrument may be a useful tool in studies of the associations between tea consumption, tea polyphenols intake, and risk for chronic disease.

Development of heparin antagonists with focused biological activity.

Heparin, a complex glycosaminoglycan, has long been used to temporarily render the blood incoagulable during extracorporeal circulation, cardiovascular surgery, and other arterial interventions. But bleeding complications are especially common when the arterial tree is violated, occurring in as many as 10-15% of cases. For cardiovascular surgery and many related interventions, protamine has long been the standard antagonist when acute and complete neutralization of heparin s anticoagulant effect is necessary. Protamine s efficacy is related in part to its total net cationic charge, but unfortunately so is its toxicity. For these reasons, there is renewed interest in developing heparin antagonists which will replace the use of protamine. At Commonwealth Biotechnologies, Inc., we have used a rationale design approach for the preparation of a family of low molecular weight helix peptides which bind heparin with high affinity. For each of the new compounds, we have assessed their ability to bind heparin using isothermal titration calorimetry and circular dichroism spectrometry and have examined potential complexes formed with the anticoagulant pentasaccharide unit of heparin using molecular modeling techniques. The biological potencies of these compounds were assessed in ex vivo experiments where their ability to compete with antithrombin for binding heparin was determined. The best of the compounds, designated HepArrestTM, is highly effective in reversing heparin-mediated and HepArrest is a safer drug than protamine because of reduced adverse hemodynamic side effects compared with those associated with protamine. HepArrest binds low molecular weight heparins and causes reversal of anticoagulation by low molecular weight heparins, as determined by activated partial thromboplastin time, thrombin time, or factor Xa neutralization assays. These highly promising preclinical results indicate that HepArrest is a novel heparin neutralizing agent that may well fill a substantial unmet need for vascular surgeons and cardiac anesthesiologists who perform coronary artery bypass grafts and several other major vascular surgeries, as well as for cardiologists and interventional radiologists.